This RFA is intended to address "those factors affecting the safe and effective use of iron interventions for the prevention and treatment of iron deficiency and anemia in women of reproductive age (including adolescent girls), infants, and children, particularly in areas of endemic malaria." The current application specifically addresses the terms of the RFA by proposing the use of encapsulated ferrous fumarate, supplied in a powder form with other essential micronutrients as a potentially safer and effective alternative to syrups or drops for providing iron to infants and young children living in regions where the burden of malaria is high. Thus, the primary objective of this research application is to determine the impact of providing powdered encapsulated iron added to complementary foods on the susceptibility to clinical malaria among anemic and non-anemic infants and young children (6-24 months of age) living in a high malaria burden area (Northern Ghana). A community-based blinded randomized controlled trial will be conducted in two phases: Phase I will take place during the dry season, when malaria transmission rates are lower. Eligible subjects will be individually randomized to receive a daily dose of either a powdered vitamin/mineral fortificant containing 7.5 mg of iron, or a placebo (containing all micronutrients excluding iron), added to complementary foods, for 5 months. Phase II will include a unique cohort of subjects and take place during the wet season, when malaria transmission rates are higher. All other aspects of the protocol will be similar to Phase I. Certain secondary variables that may influence the primary outcome, such as iron status and breastfeeding rates, will be concurrently measured throughout the intervention periods. The secondary objectives are to determine the impact of 'point-of-use'iron fortification on the severity of clinical malaria by documenting parasite counts and hospital admission rates, as well as differences in secondary complications of malaria infections, such as death, cerebral malaria, pneumonia, dehydration, and diarrhea. The long term goal of the proposed research is to develop new evidence to inform global policy and guide the implementation of programs to prevent and treat iron deficiency disorders in malaria endemic regions. PUBLIC HEALTH RELEVANCE: It is anticipated that the proposed research will provide important information for addressing factors affecting the safe and effective use of iron interventions for the prevention and treatment of iron deficiency and anemia in children in areas of endemic malaria.